Genetic Components of 25-Hydroxyvitamin D Increase in Three Randomized Controlled Trials.

Olivia Trummer,Barbara Obermayer-Pietsch,Wilfried Renner,Natascha Schweighofer,Stefan Pilz,Martin Grübler,Elisabeth Lerchbaum,Verena Theiler-Schwetz,Martin H Keppel,Christoph W Haudum,Thomas R Pieber,Christian Trummer

doi:10.3390/jcm9020570

Abstract

The 25-Hydroxyvitamin D (25[OH)D) serum concentration depends on vitamin D intake, endogenous vitamin D production and genetic factors. The latter have been demonstrated in large genome-wide association studies indicating that single nucleotide polymorphisms (SNPs) in genes related to the vitamin D metabolism are as important for serum 25(OH)D levels as the influence of season. The mechanism on how these SNPs influence serum 25(OH)D levels are still unclear. The aim of the present study was to investigate the genetic effects of ten selected SNPs related to vitamin D metabolism on 25-hydroxyvitamin D increase (∆25(OH)D) after vitamin D supplementation in three randomized controlled trials. Genotypes of SNPs related to vitamin D metabolism were determined in 411 participants with 25(OH)D concentrations < 75 nmol/l receiving 20,000 IU cholecalciferol per week for 8 or 12 weeks after study inclusion. For the vitamin D receptor (VDR) rs10783219 polymorphism, the minor A-allele was associated with lower ∆25(OH)D values in the entire study population (p = 0.022), which was not consistent in all three cohorts when analysed separately. VDR rs10783219 might therefore be a genetic modulator of increasing 25-hydroxyvitamin D concentrations. Considering the wide-spread use of vitamin D supplementation, future large and well-designed randomized controlled trials (RCTs) should investigate the clinical impact of this polymorphism.

Highlights

Vitamin D is known for its fundamental role in calcium and bone metabolism [1,2]
We present data of 10 polymorphisms out of 6 genes analysed in 411 participants with 25(OH)D levels < 75 nmol/l participating in vitamin D RCTs who were allocated to the intervention group
We identified vitamin D receptors (VDRs) rs10783219 as a genetic variant associated with lower ∆25(OH)D levels after vitamin D supplementation

Summary

Introduction

Vitamin D is known for its fundamental role in calcium and bone metabolism [1,2]. Due to the fact that the vitamin D receptor (VDR) is expressed in almost every tissue and cell throughout the human body, there have been extensive investigations on potential extra-skeletal effects of vitamin D [3]. Randomized controlled trials (RCTs) have largely failed to show significant effects of vitamin D supplementation on various health outcomes [3] and Mendelian randomization studies suggested that low 25(OH)D concentrations in the respective studies might be prone to reversed causality, i.e., being consequences rather than causes for associations like mortality [6] or cancer [7]. This does not invalidate the potential predictive power of 25(OH)D concentrations for these associations

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